SNP

Nearest gene

Effect allele/ Other allele

Favorable Energy Balance Group

Unfavorable Energy Balance Group


Direct effect

Indirect effect

Total effect

Direct effect

Indirect effect

Total effect


CRC risk in relation to SNP through pathways other than HOMAIR

CRC risk in relation to SNP through HOMAIR

CRC risk in relation to SNP

CRC risk in relation to SNP through pathways other than HOMAIR

CRC risk in relation to SNP through HOMAIR

CRC risk in relation to SNP


HR^{a}

95% CI

Effect size^{a}

95% CI

HR^{a}

95% CI

HR^{a}

95% CI

Effect size^{a}

95% CI

HR^{a}

95% CI


BMI^{b}

rs2191349

DGKB/TMEM195

G/T

1.04

(0.84–1.28)

<0.001

(−0.004–0.004)

1.07

(0.90–1.28)

1.45

(1.03–2.03)

<0.001

(−0.003–0.003)

1.17

(0.90–1.52)

rs4607517

GCK

G/A

0.79

(0.61–1.03)

<0.001

(−0.01–0.01)

0.80

(0.64–1.00)

1.04

(0.66–1.62)

<0.001

(−0.004–0.003)

1.06

(0.75–1.51)

rs174550

FADS1

T/C

1.16

(0.93–1.45)

<0.001

(−0.001–0.001)

1.05

(0.87–1.27)

1.40

(0.96–2.04)

−0.01

(−0.02–0.01)

1.37

(1.02–1.83)

rs11605924

CRY2

C/A

0.87

(0.71–1.07)

<0.001

(−0.01–0.01)

0.82

(0.69–0.98)

1.32

(0.93–1.87)

<0.001

(−0.003–0.003)

1.07

(0.82–1.39)

Waist^{c}

rs2191349

DGKB/TMEM195

G/T

0.97

(0.76–1.23)

0.002

(−0.01–0.01)

1.00

(0.81–1.23)

1.37

(1.05–1.79)

−0.002

(−0.004–0.01)

1.20

(0.97–1.48)

rs174550

FADS1

T/C

1.22

(0.94–1.58)

−0.002

(−0.01–0.01)

1.03

(0.83–1.28)

1.24

(0.93–1.65)

−0.01

(−0.02–0.002)

1.25

(1.00–1.57)

rs11605924

CRY2

C/A

0.84

(0.67–1.06)

<0.001

(−0.01–0.01)

0.81

(0.66–0.99)

1.17

(0.90–1.54)

<0.001

(−0.01–0.01)

0.97

(0.79–1.20)

Waist/hip Ratio^{d}

rs2191349

DGKB/TMEM195

G/T

1.04

(0.84–1.29)

0.003

(−0.01–0.004)

1.03

(0.86–1.23)

1.38

(1.00–1.89)

<0.001

(−0.01–0.01)

1.24

(0.97–1.59)

rs10885122

ADRA2A

G/T

0.78

(0.58–1.05)

<0.001

(−0.01–0.01)

0.84

(0.64–1.08)

1.31

(0.77–2.20)

<0.001

(−0.01–0.01)

1.58

(1.01–2.48)

rs174550

FADS1

T/C

1.15

(0.92–1.45)

0.002

(−0.004–0.01)

1.08

(0.89–1.30)

1.43

(1.01–2.03)

−0.008

(−0.02–0.004)

1.27

(0.97–1.66)

Physical activity level^{e}

rs4607517

GCK

G/A

0.73

(0.52–1.01)

<0.001

(−0.003–0.003)

0.72

(0.55–0.95)

0.95

(0.69–1.31)

−0.001

(−0.01–0.004)

0.99

(0.76–1.28)

Dietary fat intake^{f}

rs4607517

GCK

G/A

0.92

(0.72–1.18)

<0.001

(−0.01–0.004)

0.94

(0.76–1.17)

0.58

(0.33–1.03)

−0.001

(−0.01–0.001)

0.66

(0.43–1.00)

rs11558471

SLC30A8

A/G

1.08

(0.88–1.33)

<0.001

(−0.01–0.01)

0.95

(0.80–1.12)

1.64

(0.94–2.85)

−0.003

(−0.01–0.01)

1.60

(1.07–2.40)


BMI body mass index, CI confidence interval, CRC colorectal cancer, HOMAIR homeostatic model assessment–insulin resistance, HR hazard ratio, SNP single–nucleotide polymorphism, w/h ratio waisttohip ratio

Note: Proportions explained by HOMAIR for SNP–CRC risk association for rs2191349 (42.8%, 2.0%, and 33.3% among nonobese group [BMI < 30, waist ≤88 cm, w/h ≤ 0.85, respectively]; N/A [> 100%], 85.0%, and 58.3% among obesegroup [BMI ≥ 30, waist >88 cm, w/h > 0.85, respectively]), for rs4607517 (0.4%, 0.7%, and 2.7% among nonobese group [BMI < 30, MET ≥10, and <40% calories from fat, respectively]; 42.8%, 3.6%, and 10.9% among obesegroup [BMI ≥ 30, MET <10, and ≥40% calories from fat, respectively]), for rs174550 (N/A [> 100%], N/A [> 100%], and N/A[> 100%] among nonobese group [BMI < 30, waist ≤88 cm, and w/h ≤ 0.85, respectively]; 8.7%, 6.3%, and 63.3% among obesegroup [BMI ≥ 30, waist >88 cm, and w/h > 0.85, respectively]), for rs11605924 (6.1% and 3.7% among nonobese group [BMI < 30 and waist ≤88 cm, respectively]; N/A [> 100%] and N/A [> 100%] among obesegroup [BMI ≥ 30 and waist >88 cm, respectively]), for rs10885122 (6.7% in w/h ≤ 0.85; 47.6% in w/h > 0.85), and for rs11558471 (13.8% in <40% calories from fat; 5.7% in ≥40% calories from fat). Only SNPs having statistically significant results are included. Numbers in bold face are statistically significant

^{a}Multivariate regression was adjusted by covariates (age, education, family history of diabetes mellitus, family history of colorectal cancer, cardiovascular disease ever, hypertension ever, high cholesterol requiring pills ever, total Healthy Eating Index2005 score, dietary alcohol and total sugars per day, smoking status, lifetime partner, depressive symptom, oral contraceptive use, history of hysterectomy or oophorectomy, age at menarche, age at menopause, pregnancy history, breastfeeding at least 1 month, and hormone therapy); effectmodifier variables (physical activity, BMI, and w/h ratio), when not evaluated as effect modifier variables, were adjusted as a covariate; when stratified via waist circumference, w/h ratio was not adjusted

^{b}Participants stratified by BMI as nonobese (BMI < 30, n = 3675) or obese (BMI ≥ 30, n = 1704); interaction tests presented for the effect of BMI on the association between CRC and rs2191349 (effect size −0.10, pvalue 0.70), rs4607517 (effect size −0.30, pvalue 0.65), rs174550 (effect size −0.70, pvalue 0.09), and rs11605924 (effect size −0.38, pvalue 0.15)

^{c}Participants stratified by waist circumference as nonobese (waist ≤88 cm; n = 3042) or obese (waist >88 cm; n = 2337); interaction tests presented for the effect of waist circumference on the association between CRC and rs2191349 (effect size −0.21, pvalue 0.38), rs174550 (effect size −0.89, pvalue 0.01), and rs11605924 (effect size −0.42, pvalue 0.09)

^{d}Participants stratified by w/h as nonobese (w/h ≤ 0.85; n = 3712) or obese (w/h > 0.85; n = 1667); interaction tests presented for the effect of w/h on the association between CRC and rs2191349 (effect size −0.21, pvalue 0.40), rs10885122 (effect size 0.59, pvalue 0.02), and rs174550 (effect size −0.34, pvalue 0.34)

^{e}Participants stratified by physical activity level as nonobese (MET ≥10; n = 2344) or obese (MET <10; n = 3035); interaction test presented for the effect of physical activity on the association between CRC and rs4607517 (effect size 0.94, pvalue 0.14)

^{f}Participants stratified by dietary fat intake as nonobese (< 40% calories from fat; n = 4325) or obese (≥ 40% calories from fat; n = 1054); interaction tests presented for the effect of dietary fat intake on the association between CRC and rs4607517 (effect size 1.45, pvalue 0.01) and rs11558471 (effect size −1.53, pvalue 0.04)